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151.
W J Scott C A Duggan C M Schreiner M D Collins 《Toxicology and applied pharmacology》1990,103(2):238-254
The effects of acetazolamide on the developing rodent limb bud were postulated to result from a reduction of intracellular pH (pHi). Embryonic intracellular pH was calculated from transplacental distribution of the weak acid, 5,5'-dimethyloxazolidine-2,4-dione, in teratogenically sensitive (C57BL/6) and resistant (SWV) inbred mice. pHi was reduced by acetazolamide treatment in C57 embryos and limb buds but not in SWV samples. Acetazolamide teratogenesis can be exacerbated by coadministration of amiloride, presumably through inhibition of Na+/H+ exchange attributable to the latter agent. pHi reduction after such treatment was more profound than after acetazolamide alone, providing further support for the central hypothesis. pH was also reduced in other embryonic (embryo plasma) and extraembryonic compartments (exocoelomic fluid, amniotic fluid). pH changes in these compartments could also lead or contribute to abnormal development. 相似文献
152.
Reversal of diabetes in BB rats by transplantation of encapsulated pancreatic islets 总被引:8,自引:0,他引:8
Prolonged survival of pancreatic islet allografts implanted in diabetic BB rats was achieved by encapsulation of individual islets in a protective biocompatible alginate-polylysine-alginate membrane without immunosuppression. Intraperitoneal transplantation of the encapsulated islets reversed the diabetic state of the recipients within 3 days and maintained normoglycemia for 190 days. Normal body weight and urine volume were maintained during this period, and no cataracts were detected in the transplant recipients. In contrast, control rats receiving transplants of unencapsulated islets experienced normoglycemia for less than 2 wk. These results demonstrated that microencapsulation can protect allografted islets from both graft rejection and autoimmune destruction without immunosuppression in an animal model that mimics human insulin-dependent diabetes. 相似文献
153.
E Nakano T Yoshioka M Matsuda T Sonoda H Yano Y Ihara H Kuroda T Kishimoto T Sakurai K Uchida 《Hinyokika kiyo. Acta urologica Japonica》1990,36(5):635-642
Clinical effect of LM-001, a prostaglandin synthetic inhibitor developed from a drug delivery system, was evaluated in 54 patients with pain from urinary tract stones (stone pain) and 32 with vesical urgency after an operation on bladder or prostate. LM-001, felbinac ethyl incorporated in lipid microsphere, wes intravenously administered at the onset of stone pain or vesical urgency. Of 54 with stones and 32 with urgency, 53 and 29 were eligible for response, respectively. The symptoms improved or disappeared in some cases just after the administration and in the majority of patients within 15 minutes, in 49 of 53 patients with stone pain. Further, the effectiveness lasted over 24 hours in 26 of the 49 responding to this agent. On one hand, improvement or disappearance of vesical urgency was recognized in 25 of 29 patients, and the effectiveness was observed shortly after injection in 16 and lasted over 24 hours in 13 cases. Toxicities of this drug were investigated in 54 patients with stone pain and 32 with urinary urgency. Side effects consisted of pain at the injection site in 4, a slight fall of blood pressure in 1, slight visual disturbance in 1, body heat sensation in 1, leukocytosis in 3 and elevation of alkaline phosphatase in 1. These symptoms were transient and disappeared without use of any agent. LM-001 is concluded to be a useful drug for controlling stone pain and vesical urgency since an immediate effect, long durability and high response rates were obtained without severe side 相似文献
154.
K. Nishiyama S. Murayama Y. Nishimura K. Asayama I. Kanazawa 《Acta neuropathologica》1996,93(1):19-23
Iron accumulation in the basal ganglia and spheroid formation are pathological hallmarks of Hallervorden-Spatz disease (HS).
Since an overaccumulation of iron (iron thesaurosis) that exceeds the binding capacity of ferritin could cause oxidative damage,
we studied the possible role of oxidative stress in the pathogenesis of HS. The basal ganglia and spinal cord from patients
with HS were investigated at autopsy, using histochemistry for iron and immunohistochemistry for Cu/Zn superoxide dismutase
(SOD1), Mn superoxide dismutase (SOD2) and ferritin. SOD1-like immunoreactivity (IR), SOD2-IR and ferritin-IR occurred frequently
in spheroids observed in the basal ganglia, and associated iron accumulation indicated the possible existence of increased
oxidative stress in HS patients. Spheroids in the spinal cord showed intense SOD1-IR and SOD2-IR in HS, in sharp contrast
with the occasional weak SOD1-IR and SOD2-IR observed in spheroids from patients with amyotrophic lateral sclerosis (ALS).
Neither increased ferritin-IR nor iron accumulation were observed in spinal spheroids from HS and ALS patients. These data
may suggest that, at least in the spinal cord, SOD1-IR and SOD2-IR in spheroids in HS patients do not result from oxidative
stress directly related to iron accumulation.
Received: 15 March 1996 / Revised accepted: 15 July 1996 相似文献
155.
Dual effects of chlorobutanol on secretory response and intracellular Ca2+ dynamics in isolated pancreatic acini of the rat. 下载免费PDF全文
1. The effects of chlorobutanol, a widely used drug preservative, on exocrine response and intracellular Ca2+ dynamics were examined in isolated pancreatic acini of the rat. 2. Chlorobutanol (1 mg ml-1) markedly inhibited the secretory response to cholecystokinin octapeptide (CCK-8), carbamylcholine chloride (carbachol), or sodium fluoride, a direct G-protein activator. However, chlorobutanol itself induced a maximal release of amylase when the dose was increased to 4 mg ml-1. 3. An oscillatory fluctuation of cytoplasmic Ca2+ concentration, [Ca2+]c, induced by 5 pM CCK-8 or 0.3 microM carbachol was totally abolished in the presence of 1 mg ml-1 chlorobutanol. 4. A biphasic change in [Ca2+]c induced by 100 pM CCK-8, a rapid rise followed by a gradual decay, was transformed to an oscillatory fluctuation by the preservative. 5. Chlorobutanol inhibited 13 pM [125I]-CCK-8 or 0.5 nM [3H]-methylscopolamine chloride binding to the acinar cells in a dose-dependent manner. 6. These results indicate that chlorobutanol produces discernible pharmacological effects on the secretory response in rat pancreatic acinar cells through changes in the Ca2+ dynamics. Possible sites of action could be at a binding process of secretagogues to their receptors, at an activation process of a G-protein located in the plasma membrane, or at the processes following G-protein activation. However, the possibility that the preservative may distort the Ca(2+)-transport function of the plasma membrane or the membrane of intracellular organella, especially Ca(2+)-sequestering pools, cannot be excluded. 相似文献
156.
1-乙基-6-氟-1,4-二氢-4-氧代-7-(4-芳酰硫代氨甲酰基-1-哌嗪基)-3-喹啉羧酸的合成及抗菌作用 总被引:4,自引:1,他引:3
Thirteen new 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-aroyl-thiocarbamoyl- 1 piperazinyl)-3-quinoline carboxylic acids were prepared, Their structures were characterized by elemental analysis, IR, HNMR and MS spectra.Preliminary pharmacological tests indicated that some of compounds Ia~m possess strong inhibiting activity against Escherichia coli, Bacillus subtilis and Proteus at concentration of 100 μg/ml. 相似文献
157.
T Oda N Yoshizawa S Oshima A Takeuchi T Kubota S Kondo Y Oshikawa Y Akashi Y Suzuki H Niwa 《Nihon Jinzo Gakkai shi》1990,32(6):631-641
To investigate the role of cell-mediated immunity (CMI) in glomerulonephritis (GN), we identified the infiltrating immune cells both within the glomerulus and in the interstitium. Frozen sections from 103 patients with various forms of GN: 10 with minor glomerular abnormality (MGA) as control, 10 with minimal change nephrotic syndrome (MCNS), 10 with membranous nephropathy (MN), 9 with focal glomerulosclerosis (FGS), 30 with IgA nephropathy (IgAN), 22 with acute post streptococcal glomerulonephritis (APSGN), and 2 with rapidly progressive glomerulonephritis (RPGN) were examined using monoclonal antibodies (MoAb) by indirect immunoalkaline-phosphatase labelling. In most glomerulonephritis, monocyte/M phi and helper/inducer T cells were predominantly infiltrating in the interstitium, but intraglomerular infiltration was rare, except for APSGN. This interstitial infiltration increased proportionally to the level of serum creatinine, and was most prominent in RPGN. Apparently different distribution was seen in APSGN, that is, prominent increase in total number of intra-glomerular monocyte/M phi infiltration with slightly increased T cells. The change was correlated with time after onset; namely the more leucocytic infiltration was observed when the tissue was taken earlier. These data suggest that in APSGN, monocyte/M phi accumulate in glomeruli via cell mediated immunity in addition to humoral immune mechanism resulting in glomerular hypercellularity, whereas in most chronic glomerulonephritis interstitial leucocyte infiltration, particularly helper T cells and monocyte/M phi may play an important role in the progression of glomerulonephritis. 相似文献
158.
159.
T Uno H Kondo Y Inoue Y Kawahata M Sotomura K Iuchi G Tsukamoto 《Journal of medicinal chemistry》1990,33(10):2929-2932
A series of novel pyridone carboxylic acids having a 4-hydroxypiperazinyl group at the 7-position of norfloxacin and ciprofloxacin were prepared. The in vivo antibacterial efficacies of these compounds were superior to those of corresponding piperazinyl derivatives. From the results of the studies on the pharmacokinetic profile and toxicity, the 4-hydroxypiperazinyl derivatives were confirmed to be pharmacologically superior to corresponding piperazinyl derivatives. Thus, a 4-hydroxypiperazinyl group was revealed to be a beneficial substituent for potential use in future quinolone antibacterials. 相似文献
160.
D Y Graham 《Mayo Clinic proceedings. Mayo Clinic》1988,63(12):1258-1260
Occurrence of C. pylori infection of mucosa outside of the stomach might provide an ideal opportunity to examine C. pylori-mucosal interactions apart from the effects of acid and pepsin. Techniques previously used to examine Barrett's epithelium (for example, special mucin stains or scanning and transmission electron microscopy) might be particularly useful for exploration of new associations and formulation of new hypotheses. Whether C. pylori has a role in development of Barrett's ulcer or adenocarcinoma as a complication of Barrett's esophagus remains unanswered. Most of the current data about C. pylori are primarily observational; further studies are needed for clarification of important microbegut interactions. 相似文献